Reflex Sympathetic Dystrophy

Complex Regional Pain Syndrome (CRPS)

Edward Carden, M.D., FRCP(C)

Fellow, American Academy of Pain Management

Clinical Professor, University of Southern California School of Medicine Director Southern California Academic Pain Management

1508 Arizona Ave, Santa Monica , CA 90404

In this paper I am going to explain, in laymen’s terms, Reflex SympatheticDystrophy (RSD), its pathology, the new taxonomy (which includes ComplexRegional Pain Syndrome, sympathetically maintained pain, sympatheticallyindependent pain, and causalgia), and the rules for diagnosing these various andsundry neuropathic pain conditions, together with current methods of treatment.

Definition

The term RSD was first used by Evans in 1946 but has been applied to describe variousclinical syndromes, such as Sudeck’s atrophy, traumatic arthritis, minor causalgia, post-traumatic osteoporosis, post-traumatic pain syndrome, post-traumatic edema, post-traumatic angiospasm, shoulder-hand syndrome, etc. It was defined by the InternationalAssociation for the Study of Pain as continuous pain in a portion of an extremity aftertrauma, which may include fracture but does not involve major nerves. It is associatedwith sympathetic nervous system changes but is not a disease of the sympathetic nervoussystem. Causalgia is left as a separate syndrome, although the symptoms and clinicalpresentation of the conditions overlap, as do their treatments. Pathology of causalgia is,by definition, damage to a major nerve trunk, whereas with RSD there is usually damageto some very minor nerves. It may also appear after certain medical problems, which willbe noted later.

Clinical features and findings

Clinical features are symptoms and changes, which often start at the site of theprecipitating event, presenting with a glove-and-stocking anatomical distribution (with adistribution just like a glove or a stocking) which does not usually follow dermatomallines (areas of the body supplied by one spinal nerve.)

Clinical findings include: disturbances of autonomic (sympathetic system) regulationwith alterations in blood flow; hyper- or hypohidrosis (sweating or dry skin); edema(swelling); sensory abnormalities, with hyper- or hypoesthesia (increased or decreasedsensitivity of the skin); allodynia (extreme pain to the slightest stimulation) to mechanicalor cold stimulation; motor dysfunction, with weakness or tremor; joint stiffness; trophic(degeneration) changes of the skin, hair and nails, and psychological reactivedisturbances (including anxiety, depression or hopelessness).

The physiologic features manifest diffusely but not necessarily uniformly in the entiredistal extremity; they may occur anytime after the onset of the syndrome, spreadingproximally (towards the body) and distally (towards the feet or hands) and occasionallyto other extremities as the syndrome progresses. Dominating symptoms are spontaneouspain, swelling, weakness and loss of function.)

Disease stages

There are three stages of RSD defined by deTakats, with later modifications by Bonica.RSD does not necessarily follow these stages, but this is a good, basic guideline fromwhich to work.

Stage I: Beginning within a few days or weeks of the precipitating event, this stage ischaracterized by pain, and often by burning, in the area of the injury. There is frequentlyhyperesthesia as well. Movement worsens pain, and immobility of the limb is obvious byits protected position. There is usually accompanying edema, tenderness of the distaljoints of the limb, and often local muscle spasm as well. The limb may be warm, red, anddry or cool and pale. This phase may resolve spontaneously or should respond rapidly tothe appropriate treatment modality. The clinical picture varies from a few days to a fewmonths.

Stage II: As the RSD progresses, pain can increase or decrease or remain unchanged.There may be beginnings of local hyperesthesia, paraesthesia (abnormal sensations), orallodynia. Edema spreads, local joints become stiff, muscle wasting in the region of theinjury begins, and the skin may become cold, pale, cyanotic, and moist. The hair of theaffected limb may become thickened and coarse. Also, the nails may become brittle.Osteoporosis progresses to a diffused form and increased blood flow on scintigraphy (aspecial X ray procedure) is seen. Appropriate treatments can still be effective, thoughpatients in this stage will be more difficult to cure.

Stage III: This stage is marked by severe trophic changes and resistance to treatment. Thepain is variable, with increased spreading allodynia and disesthesia (mistaken sense ofsensation, e.g. soft touch feels prickly.) The pain is usually a burning discomfort, whichis often aching or throbbing. Exposure to cold air or a draft may aggravate the pain, asmay damp weather. Extreme immobility of the limb is often present, and the there maybe ankylosis (complete immobility) of the joints, partly due to atrophy and contractingmuscles. Often the edema has resolved with subcutaneous tissues becoming atrophied.The skin is smooth and shiny, cold, and often damp. The nails and hair are thickened andbrittle. These patients are often anxious, tentative, and depressed, with all the vegetativesymptoms of that state. X-ray examination will show diffuse osteoporosis (thinning of thebones). More advanced forms of treatment are needed to help patients with this sort ofproblem.

Causalgia can present in exactly the same way in all three stages.

Sympathetically maintained pain (SMP)

One of the factors common to RSD and causalgia is that almost all patients will respondto sympathetic blockade (blockage of the sympathetic nerves supplying the area withlocal anesthetics), which will take away their pain for a variable length of time. However,many patients do not present with the full-blown syndrome that includes all the signslisted above, but do respond to a sympathetic blockade. These patients’ problem fits intothe category called sympathetically maintained pain.

For example, a patient may come to a doctor with pain only. There may not be allodynia,there may not be swelling, there may not be muscle spasms or any of the other factorsrelevant to the diagnosis of RSD. However, a sympathetic blockade takes away theirpain. In fact, patients can present with any of the symptoms of RSD on their own. Theycan present with just swelling, just allodynia, just burning pain, muscle spasm, etc., and ifthese people respond to sympathetic blocks, they are then defined as havingsympathetically maintained pain or sympathetically maintained pain syndrome.

Sympathetically independent pain (SIP)

Some patients will present with the classic symptoms of RSD; however, sympatheticblockade does not take away their pain. This may be due in part to a disease process thatwe don’t understand, or it may be that these patients have progressed so far along in theirdisease that the disease has become centrally maintained only (there are now changes inthe nerve cells in the spinal cord), and sympathetic blocks have little or no effect on itwhatsoever. Often in Stage III of RSD, patients start to suffer from SIP.

Complex Regional Pain Syndrome

There has been dissatisfaction with the term reflex sympathetic dystrophy. In 1995,therefore, a new taxonomy was formulated to include the terms complex regional painsyndrome Type I (formerly reflex sympathetic dystrophy) and complex regional painsyndrome Type II (formerly causalgia.)

Complex regional pain syndrome (CRPS) is a term that describes a variety of painfulconditions which can follow injury, appearing regionally and having a distalpredominance of abnormal findings that exceed in both magnitude and duration theexpected clinical course of the inciting event. Such condition often results in significantimpairment of motor function.

CRPS Type I (RSD)

In this syndrome, which develops after an initiating noxious event, continuing pain orallodynia/hyperalgesia occurs. It is not limited to the distribution of a single peripheralnerve, and it is disproportionate to the inciting event. There is or has been evidence ofedema, skin blood flow abnormality, or abnormal sudomotor (sweating) activity in theregion of the pain. If other conditions exist that would otherwise account for the degree ofpain and dysfunction, this diagnosis is excluded.

CRPS Type II (Causalgia)

This syndrome develops after a nerve injury.

Sympathetically maintained pain (SMP)

Pain that is maintained by sympathetic efferent innervation or by circulatingcatecholamines (epinephrine and norepinephrine), SMP may be a feature of several typesof painful conditions and is not an essential requirement of any one condition.

Pathophysiology

The hallmark of RSD is ongoing pain and allodynia, which is typically out of proportionto the injury. The causative event can vary widely from trivial injury to major trauma, orthere may be no significant trauma at all. A theory proposed by Roberts, one whichincorporates many of the observations noted in these patients, suggests that the allodyniaand spontaneous ongoing pain in RSD is the result of a chronic maladaptive sensitizationof wide dynamic range neurons (nerve cells) in the dorsal horn of the spinal cord, and is

not a heightened sympathetic tone. There is, however, a connection between thesympathetic system and these wide dynamic range neurons.

The output from the skin touch receptors, (low threshold mechanoreceptors), is via largediameter A beta nerve fibers, and this is influenced by activity of the sympathetic nervesin the area. These touch receptors discharge afferent impulses (messages to the spinalcord) that maintain at a rate proportional to the sympathetic tone. Under normalcircumstances, these sensory invoked impulses from touch fibers have insufficientmagnitude to provoke a response from the wide dynamic range cells. However, when awide dynamic range cell becomes sensitized (as happens following an injury and in RSD,SMP, et.), the threshold of stimulation falls sufficiently so that it responds to thesympathetically maintained impulses evoked from nociceptive afferent A beta fibers andconverts this information to noxious (unpleasant sensory) impulses destined for the brain.If the level of norepinephrine (which is normally secreted by the sympathetic nerves)circulating in the area of the mechanoreceptors is reduced, then their output is reducedand the pain goes away.

This is how sympathetic blockade takes away the pain of RSD and sympatheticallymaintained pain syndromes. Injection of norepinephrine to these areas makes the painworse. This theory does not explain all the things that occur with RSD andsympathetically maintained pain. But this is good basic theory from which to work. It isthought that as the disease progresses due to the barrage of impulses coming in from theperiphery into the dorsal horn, cell death occurs to cells in the dorsal horn and chronicpain state develops that now may not respond to sympathetic blockade. This is calledsympathetic independent pain (SIP). This is a relatively simplistic view but serves tocover the majority of the evidence we have at this time.

Diagnosis of RSD

First of all, the presentation will be burning pain, allodynia, possible muscle spasm, andlancinating (shooting) pain, as well as a temperature and all possible color changes in theextremity, edema, and skin, hair and nail growth changes. The patient may have one orall of these symptoms. By the time skin, hair and nail growth changes are seen, it’s a signthat somebody has missed the diagnosis, and the patient is proceeding into a chronic painstate. It is interesting to note here that the typical RSD patient will be able to tell youwhen it’s going to rain with greater predictive accuracy than the weather service, sincepain begins to get worse as rain approaches. The patient is also likely to have pain that isnot easily controlled with systemic narcotics and have greater difficulty sleeping becausethe pain gets worse at night.

Clinical Testing

The backbone test for this disease is a sympathetic block. In over 95% of patients, theblockade will take away their pain.

Additional tests are:

1. Thermography2. Quantitative sweat test3. Triple phase bone scan4. Cold and mechanical allodynia5. IV phentolamine test

Incidence and epidemiology

Various papers have been published on the incidence and causality of RSD in the generalpopulation. Most of the cases of causalgia were in adult males aged 20 to 40, becausethey had received bullet wounds in combat, but as regards RSD, there is a tendency formore patients to be women than men and to be in the 20 to 50 age group (although RSDhas occurred in children and in people over 70).

Blunt trauma may cause RSD, as may myocardial infarction (heart attack), with a fewpapers published reporting patients with RSD of the hand, and either shoulder-handsyndrome or RSD of the hand following myocardial infarction. It may also occur afterischemic heart disease, radiculopathy (irritation or injury to a single spinal nerve), spinalcord injuries, CVA’s (strokes0, diabetic neuropathy, cancer, multiple sclerosis, cerebrallesions, infections and vascular disease. RSD-type symptoms are seen very commonlyafter wrist fractures. This is possibly due to damage to the median nerve that carries mostof the sympathetic fibers to the hand. This is usually a self-limiting disease, but it iscommonly noted that people with wrist fractures have a very difficult time rehabilitatingtheir wrists with physical therapy and seem to have excessive amounts of pain. Thesepeople respond very well to a few sympathetic blocks done just before physical therapy,and this enables them to resume full use of their wrist sooner.

The spread of RSD

RSD and sympathetically maintained pain syndromes do spread, usually to a contralateral (the opposite side) limb. This supposedly occurs in 25% of cases, if left untreated.They can also spread up the spine from a leg to an arm, and they commonly spread froman arm up into the head, typically with headaches, sinus problems, or malfunctioning ofthe eye. Since the cervical sympathetic chain is involved, cardiac problems can also occurwith syncopal (fainting) attacks and angina-type syndromes (chest pain.)

Treatment

1. Physiotherapy2. Sympathetic blockade

3. Medications4. Tens unit5. Acupuncture6. Biofeedback7. Psychotherapy8. Removal of trigger areas9. Sympathectomy10. Dorsal column stimulators11. Intrathecal (intraspinal) narcotics

The primary modalities for treatment for RSD and sympathetically maintained painsyndromes are physiotherapy and sympathetic blockade. Commonly we will do asympathetic block and send the patient for physical therapy. The therapy should be done,if possible, whilst the sympathetic block is working. This forms the basis for initialtreatment. Provided the patient is improving, this modality of treatment should becontinued. (Some people may have a frozen shoulder or restricted joint condition. Thismay necessitate blockade of nociceptive (those that transmit normal pain sensations) painfibers in order for the physical therapist to be able to manipulate the joints.

The primary task is to rehabilitate the joint or joints which are not functioning properly,strengthen the muscles, and do this while the sympathetic blockade is in effect and widedynamic range neurons are being rested.

1. Physiotherapy

The basis of therapy is passive range of motion and isometric strengthening. Heat (NOTice!) works in 90% of patients.

2. Sympathetic Blockade

A. Upper Extremity:

1. Stellate ganglion block2. Cervical epidural sympathetic block3. Interscalene and brachial plexus blocks4. Intravenous regional (Bier) block

B. Lower Extremity:

1. Lumbar sympathetic block2. Lumbar epidural sympathetic block3. Femoral, sciatic, or three-in-one block

4. Intravenous regional (Bier) block

C. Other blocks

1. Intravenous phentolamine infusions2. Intravenous lidocaine infusions

3. Medications; combination of:

A. Analgesics (e.g., Vicodin, morphine, fentanyl)

B. Relaxants (e.g., Soma, Baclofen)

C. Antidepressants (e.g., Elavil, Trazodone)

D. Hypnotics (e.g., chloral hydrate)

E. NSAIDS (e.g., Motrin, Voltaren, etc.)

F. Steroids (e.g., Medrol dose pack)

G. Adrenergic alpha-1 and alpha-2 blocking drugs (e.g., phentolamine, yohimbine )

H. Calcium channel blockers (e.g., Procardia)

I. Oral local anesthetics (e.g., Mexiletene)

J. Anticonvulsants (e.g. Tegretol, Neurontin)

4. Tens units

Using electrodes on the skin electric impulses are transmitted over the areas of pain .

These will sometimes help, particularly if there is nociceptive (normal pain caused byinjury) pain (e.g., following manipulating a frozen shoulder).

5. Acupuncture

This works only while the needles are inserted and being stimulated; the end results arepoor.

6. Biofeedback

This is the technique of making unconscious or involuntary bodily processes perceptibleto the senses (as by the use of an oscilloscope) in order to manipulate them by consciousmental control. Biofeedback helps 15% of patients who are in a chronic pain state. It isnot usually used in the early treatment of RSD (SMP).

7. Psychological disturbance

RSD patients are expected to be depressed in more than 75% of cases. Most of them areanxious, suffering from insomnia, irritability, agitation, and poor judgment. Thesemanifestations appear after the RSD and not before. In too many cases, patients arelabeled as malingerers, psychotic, or neurotic. In fact, this is not the case. A review of theliterature reveals no evidence indicating there is a certain personality trait thatpredisposes one to develop RSD. The changes in personality develop after thedevelopment of RSD and not before.

8. Removal of trigger areas

It may be necessary to remove a trigger zone (e.g. neuroma removal). Those commonlyfound are small neuromas (nerve tumors) on peripheral nerves, which may be removedthrough the use of:

A. SurgeryB. PhenolC. AlcoholD. Radio frequencyE. Cryoneurolysis (freezing) (the best method)

9a. Sympathectomy (surgical)

At this time, surgical sympathectomy (removal of the sympathetic nerve supply) isdiscouraged in the treatment of sympathetically maintained pain and RSD. It would seemthat logically it would work, but in practical terms, 30-50% of those who have had asympathectomy get a type of pain, which is not amenable to sympathetic blockade ortreatment, leaving them worse off than before. Also, the sympathectomy often failsbecause of all the sympathetic nerves that come across from the other side.

9b. Sympathectomy (non-surgical)

Chemical, radio frequency, and cryogenic sympathectomies are done because 1) they willallow a temporary sympathectomy to take place in the region without the post-sympathectomy pain; 2) their targets will re-grow in three to four months; and 3) theygive the wide dynamic range neurons a chance to rest and thereby help the patient tocombat the disease. It is hoped the disease will eventually burn itself out or the widedynamic range neurons will revert to their original functioning during the rest period(plasticity of the spinal cord), thereby eliminating the disease.

10. Spinal cord stimulators

Spinal cord stimulators can be used, and work well after an initial trial period with thestimulator lead in place while a stimulator is placed external to the body. If the pain isthen reduced by 70% or more, an internal stimulator is implanted subcutaneously with theelectrodes inside the spine, It is about the size of a pacemaker and functions rather like aTens unit placed over the dorsal column of the spinal cord. It causes tingling sensations tobe sent to the brain rather than pain sensations. It works somewhat similarly to theprinciple of the gate theory proposed by Melzak and Wall. These are now being usedmore commonly in the earlier stages of the disease allowing diminution of pain easierphysiotherapy and more rapid reversal of the disease process.

11. Intrathecal Narcotics

For intractable pain not amenable to any of the above, intrathecal (into the spinal fluid)infusion of narcotics may be needed, and the implantation of a morphine (or somenarcotic) pump may be necessary. It should be noted that narcotics do not work wellperipherally (i.e., by mouth or injection) on patients with sympathetically maintainedpain. However, given intrathecally, the medications do work much better. These pumpsabout the size of a small hockey puck are implanted under the skin of the abdomen andcan afford a patient with intractable R S D a much more pleasant life style.

Plan of action

1. Assume that any patient who is suffering from pain that’s excessive, given the size ofthe injury, and who possesses any of the sequelae mentioned above, has SMP or RSD.until proved otherwise.

2. Go to a good pain management specialist for diagnosis.

3. Work with the pain specialist to get blocks medications and physiotherapy done, anduse the correct forms of physiotherapy.

4. Have the RSD treated before any operations are done. Be operated on ONLY IF YOUMUST.

5. If surgery really is necessary, then it must be done under a block anesthetic tominimize the nociceptive (normal pain) input, thereby minimizing the chance of the RSDreturning. Have the pain management specialist follow postoperatively to do sympatheticblocks should the sympathetically maintained pain recur. Do expect to requiresympathetic blockades postoperatively and, very likely, during the rehabilitation period.

6. Remember, the longer RSD is left without direct medical intervention, the moredifficult is becomes to effect a short-term cure. Research is going on continually and agood RSD pain treatment center will keep you apprised of developments in thispotentially devastating disease.

7. One should always look for a precipitating factor, such as irritated median nerve with aColles’ fracture, trauma to small nerve terminals at the site of the portals afterarthroscopy. Providing that these sites can be found early and dealt with in an appropriatemanner (such as freezing a neuroma, should one have occurred), the sympatheticallymaintained pain can be rapidly eliminated.

Summary

Whenever people exhibit pain out of proportion to any injury they have suffered, itshould be assumed that the source is RSD (CRPS) or sympathetically maintained painuntil proven otherwise. RSD may well present as RSD, causalgia, or one of thecomponents of these diseases. The patient should go immediately to a pain center whichspecializes in the treatment of these conditions.

The backbone of treatment for the disease is:

BLOCKS

PHYSICAL THERAPY

DRUGS

PSYCHOLOGICAL COUNSELING